POS0717 ASSOCIATION BETWEEN CUMULATED HYDROXYCHLOROQUINE IN SYSTEMIC LUPUS ERYTHEMATOSUS AND DEVELOPMENT OF CARDIAC CONDUCTION ALTERATIONS: A MULTIPLE LOGISTIC REGRESSION ANALYSIS
Authors: A. Herrero-Morant, J. Zubiaur-Zamacola, A. Margarida-de Castro, R. Pérez-Barquín, M. Á. González-Gay, R. Blanco
Journal: Annals of the Rheumatic Diseases (2022)

Background Hydroxychloroquine (HCQ) is a widely used drug in Systemic Lupus Erythematosus (SLE). It may cause cardiac alterations which includes short term arrhythmic events (via QT interval prolongation) and medium-late term dose dependent cardiomyopathy 1 . The few research articles published on the medium-late term effects of HCQ in cardiac conduction disorder do not show relevant alterations 2-3 . Objectives To assess the effect of HCQ in cardiac conduction in a consecutive SLE population. Methods Observational, single University hospital study of all consecutive SLE patients with an electrocardiogram (EKG) at HCQ onset and at least one EKG in follow-up, with a period of at least 3 months on HCQ treatment was performed. We assessed conduction alteration (CA) by EKG, defined as atrio-ventricular block, bundle branch block or QT interval prolongation. The EKGs were gathered from the clinical history and interpreted at the beginning of the treatment and during the 15.2 years (CI95% 13.24-17.16) follow-up period. We defined cumulated HCQ (cHCQ) as the multiple of the mean annual dose of the sample. A Multiple logistic regression model, adjusted by different variables according to statistical significance and clinical relevance, was performed. Results We studied 109 (96 women/13 men) SLE patients with a mean (±SD) age of 61 ±. 2.78 years. A statistically significant association was observed between the cHCQ, and the development of CA [OR 1.1 CI95% 1.02-1.9; p = 0.011] (Table 1 &amp; Figure 1). A total of 8 covariates were included. Among them, those that had the greatest influence on the development of the primary event were previous CA [OR 4.15 CI95% 6.39-624.54; p &lt;0.01]; valvular heart disease [OR 7.15 CI95% 1.31-38.91; p = 0.023] and age [OR 1.07 95% CI 1.0-1.14; p = 0.04]. Table 1. Results of univariable and multivariable logistic regressions evaluating the association between cumulated hydroxychloroquine and the development of cardiac conduction alterations. Variable Unadjusted OR 95%CI P-value Adjusted OR 95%CI P-value Cumulated hydroxychloroquine 1.07 1.02 1.12 0.01 1.10 1.02 1.19 0.01 Covariates Previous cardiac conduction alterations 28.23 5.67 140.54 0.00 63.21 6.40 624.54 0.00 Cardiac valve disease 4.71 1.66 13.37 0.00 7.15 1.31 38.91 0.02 Age 1.06 1.02 1.10 0.00 1.07 1.00 1.14 0.04 Diabetes mellitus 3.79 1.26 11.41 0.02 3.44 0.59 20.11 0.17 Cerebrovascular disease 2.95 1.02 8.50 0.05 0.10 0.01 1.03 0.05 Chronic renal disease 6.65 1.77 24.98 0.05 4.88 0.65 36.91 0.13 Pulmonary Hypertension 6.40 0.56 73.58 0.14 3.84 0.13 114.96 0.44 Alcohol consumption 6.40 0.56 73.58 0.14 10.59 0.58 194.87 0.11 Gender 0.33 0.10 0.11 0.07 Hypertension 2.32 0.91 5.90 0.08 Dyslipemia 1.46 0.61 3.50 0.40 Obesity 1.85 0.41 8.32 0.42 Smoking 1.67 0.69 4.02 0.26 Cardiac ischaemic disease 2.08 0.33 13.16 0.44 Heart Failure 5.91 1.31 26.68 0.02 Pericarditis 2.08 0.33 13.16 0.44 OR: Odds Ratio; CI: Confidence Figure 1. Cardiac conduction alterations development according to cumulated Hydroxychloroquine dose. Conclusion According to our study, it seems to be an association between the cHCQ and development of CA regardless of other variables evaluated. Wider longitudinal studies are required with a protocolized EKG performance in successive visits to further analyze this association. References [1]Chatre C, Roubille F, Vernhet H, et al. Cardiac complications attributed to chloroquine and hydroxychloroquine: a systematic review of the literature. Drug Saf. 2018;41(10):919–931. [2]Costedoat-Chalumeau N, Hulot JS, Amoura Z, Leroux G, Lechat P, Funck-Brentano C, Piette JC. Heart conduction disorders related to antimalarials toxicity: an analysis of electrocardiograms in 85 patients treated with hydroxychloroquine for connective tissue diseases. Rheumatology (Oxford). 2007 May;46(5):808-10. [3]Godeau P, Guillevin L, Fechner J et al (1981) Disorders of conduction in lupus erythematosus. Frequency and incidence in a group of 112 patients (author’s transl). AnnMed Interne (Paris) 132:234–240. Disclosure of Interests Alba Herrero-Morant: None declared, Jon Zubiaur-Zamacola: None declared, Adrián Margarida-de Castro: None declared, Raquel Pérez-Barquín: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Roche, Sanofi, Lilly, Celgene, Sobi, and MSD, Grant/research support from: Abbvie, MSD, Janssen, and Roche, Ricardo Blanco Speakers bureau: Abbvie, Lilly, Pfizer, Roche, BMS, Janssen, and MSD, Grant/research support from: Abbvie, MSD, and Roche